The present invention relates to a device for manipulating fluids and conducting reactions, and methods using such device.
The invention described provides disposable tools for conducting a number of processes important to biotechnology-based assays, such as cell capture and concentration, cell lysis and nucleic acid capture, nucleic acid amplification reactions, and the like. The liquid handling devices of the invention can be used to isolate sample material (or control material) in an enclosed, disposable device, helping minimize cross-contamination of other assays or processes.
The invention provides a liquid handling device comprising: a cylindrical actuator cavity in a substrate, the actuator cavity intersected by two or more actuator channels; one or more chambers with an access channel adapted to connect to a separate one of actuator channels; and a actuator comprising (a) a cylindrical body having a cylinder axis and having therein a liquid-handling compartment with, arrayed along the cylinder axis, a first end and a second end, the liquid-handling compartment being closed at the second end, (b) a dispensing channel located at the second end and traversing the cylindrical body, the dispensing channel adapted to be separately aligned with the actuator channels, wherein the actuator is adapted to receive in a seal-tight manner a plunger that operates to confine an effective chamber defined by the plunger and the second end by moving toward the second end or to expand the effective chamber by moving toward the first end. Preferably, one or more of the chambers are formed within the substrate. Preferably, two or more of the chambers are within the substrate, each such chamber having an access channel adapted to connect to a separate one of actuator channels. Preferably, one or more of the chambers are enclosed at one end by a gas-selective permeable membrane so that such chambers can be filled with liquid through its access channel until gas has been removed through the gas -selective permeable membrane, and liquid can be drawn out of the chamber with the pressure equalized by gas transport through the gas-selective permeable membrane.
The invention also provides a liquid handling array comprising: two or more liquid handling; and one or more first motors for moving the actuator from one alignment of the dispersing with an actuator channel to another or with a closed segment of the actuator cavity. Preferably, there are one or more second motors for moving the plunger to expand or contract the effective chamber.
The invention further provides a method of manipulating liquids comprising: operating the actuator of the liquid handling device to align the dispensing channel with a said actuator channel; operating the plunger to move fluid from a thereby connected chamber into the actuator compartment; operating the actuator to align the dispensing channel with a second said actuator channel; and operating the plunger to move fluid from the actuator compartment to a thereby connected second said chamber.
A method of manipulating liquids comprising: providing magnetically susceptible beads having attached thereto a member of a binding pair in a chamber of the liquid handling device of the invention; introducing a liquid containing a second member of the binding pair to bind the second member to the beads; activating a magnet (e.g., by engaging an electromagnet or drawing a magnet to a location where the field is effective) to draw the beads from the access channel of the chamber; operating the actuator of the liquid handling device to align a dispensing channel with an actuator channel connected to the said access channel; and drawing the liquid out of the chamber through the access channel. The beads can be used to bind and isolate macromolecules or cells (e.g., by cell-surface.